TY - JOUR

T1 - Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial

AU - Liu, Xinxue

AU - Munro, Alasdair P. S.

AU - Feng, Shuo

AU - Janani, Leila

AU - Aley, Parvinder K.

AU - Babbage, Gavin

AU - Baxter, David

AU - Bula, Marcin

AU - Cathie, Katrina

AU - Chatterjee, Krishna

AU - Dejnirattisai, Wanwisa

AU - Dodd, Kate

AU - Enever, Yvanne

AU - Qureshi, Ehsaan

AU - Goodman, Anna L.

AU - Harndahl, Linda

AU - Haughney, John

AU - Hicks, Alexander

AU - van der Klaauw, Agatha A.

AU - Kwok, Jonathan

AU - Libri, Vincenzo

AU - Llewelyn, Martin J.

AU - McGregor, Alastair C.

AU - Minassian, Angela M.

AU - Moore, Patrick

AU - Mughal, Mehmood

AU - Mujadidi, Yama F.

AU - Holliday, Kyra

AU - Osanlou, Orod

AU - Osanlou, Rostam

AU - Owens, Daniel R.

AU - Pacurar, Mihaela

AU - Palfreeman, Adrian

AU - Pan, Daniel

AU - Rampling, Tommy

AU - Regan, Karen

AU - Saich, Stephen

AU - Serafimova, Teona

AU - Saralaya, Dinesh

AU - Screaton, Gavin R.

AU - Sharma, Sunil

AU - Sheridan, Ray

AU - Sturdy, Ann

AU - Supasa, Piyada

AU - Thomson, Emma C.

AU - Todd, Shirley

AU - Twelves, Chris

AU - Read, Robert C.

AU - Charlton, Sue

AU - Hallis, Bassam

AU - Ramsay, Mary

AU - Andrews, Nick

AU - Lambe, Teresa

AU - Nguyen-Van-Tam, Jonathan S.

AU - Cornelius, Victoria

AU - Snape, Matthew D.

AU - Faust, Saul N.

PY - 2022/6

Y1 - 2022/6

N2 - OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters.METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

AB - OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters.METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

KW - COVID-19 vaccine

KW - Third dose

KW - Heterologous boost

KW - Homologous boost

KW - Fractional dose

KW - Immunogenicity

KW - Persistence

U2 - 10.1016/j.jinf.2022.04.018

DO - 10.1016/j.jinf.2022.04.018

M3 - Article

C2 - 35405168

VL - 84

SP - 795

EP - 813

JO - Journal of Infection

JF - Journal of Infection

SN - 0163-4453

IS - 6

ER -